Basic Immunology (Lecture 2) PDF

BASIC IMMUNOLOGY (LECTURE 2) Antigens, Immunogens, Epitopes & Haptens IMMUNOLOGY UNIT FACULTY OF MEDICINE AL-MAAREFA UNIVERSITY Antigen (Ag): Is any substance that can be recognized by the immune system and react with specific antibodies and receptors on the B and T lymp...

BASIC IMMUNOLOGY (LECTURE 2) Antigens, Immunogens, Epitopes & Haptens IMMUNOLOGY UNIT FACULTY OF MEDICINE AL-MAAREFA UNIVERSITY Antigen (Ag): Is any substance that can be recognized by the immune system and react with specific antibodies and receptors on the B and T lymphocytes (BCR & TCR). Immunogen: Is a substance that can be recognized and then stimulate immune system to produce specific cellular and antibodies response. -All immunogens are antigens but not all antigens are immunogens. Example: Human chromosome injection in Laboratory animal. Anti-DNA antibodies and Anti-histon antibodies produced. Epitopes (The Antigenic Determinants):  The part of the Ag that recognized by the immune system (B & T cells receptors).  Considered the basic recognition unit of Ag.  Epitope has a 3 dimensional complementary structure to antibodies, BCR and TCR.  Ag with one epitope called monovalent Ag.  Ag with more than one epitope is called polyvalent Ag.  N Which of these antigens epitopesis polyvalent? Hapten: Small non-biologic molecules that usually Can simulate a specific immune response (antibodies production) only when conjugated with large molecules called carrier proteins. - Hapten No immune response - Carrier (protein) Anti-carrier Ab. - Hapten + carrier Anti-Hapten + Anti- carrier Antibodies. Examples: 1-Penicillin: act as a hapten which bind to RBCs → hemolysis and allergic reaction which can be lethal. 2-Formaldehyde: with skin proteins: allergic reaction.  Immunogenicity and Properties of Immunogen: Immunogenicity is the ability of immunogen to induce a specific immune response. Properties of Immunogen: 1- Foreignness. 2- Size. 3- Chemical nature 4- Complexity. 1- Foreignness: -Immune system can discriminate between foreign (non-self) and self substance. -Immune cells do not react with self Ag (tolerogen) (tolerance). 2- Size: - Molecular weight < 10,000 Dalton (10 kDa) → poor immunogen. - Increased antigen size (molecular weight)→ increased immunogenicity. 3- Chemical nature: -Proteins (polypeptide) are good immunogens n followed by carbohydrates (polysaccharide). -Steroids, nucleic acid and lipids are poor immunogens. 4- Chemical complexity: As chemical complexity increases→ immunogenicity increases. So heteropolymers are strong immunogens. Proteins are heteropolymers (different amino acids).  Epitopes Recognition: BCR TCR Types and -Free soluble, - Intracellular Ag. Characters of extracellular Ag. - Protein the Antigen - Contain external - Contain internal (Ag) with its repeated epitopes to epitopes so need Epitopes : cross link BCR. degradation before -Carbohydrate and presentation to Proteins carry epitopes stimulate T cells that interacts with integrated with MHC BCR also. Example -Soluble: bacterial - Tumor cells proteins. endotoxins. - Intracellular pathogens -Surface-bound as viruses & molecules; (e.g. Mycobacterium bacterial capsule & tuberculosis. flagella). APC Superantigen: - Is a protein produced by some pathogens. -Not up-taken nor processed by phagocyte (antigen presenting cells). - Cross link the outside groove of MHC with TCR stimulating large numbers of T cells; (Polyclonal T- cells activation)→ ↑ cytokines 10000 – 100000 times more than the normal response→ fever, systemic toxicity, skin rash, hypotension and shock. Examples: Some Bacterial Exotoxins: (Staphylococcus aureus Toxic shock antigen; cause STSS). n T-cell Dependent and T-cell Independent Antigens: Antigens are classified as either T-cell dependent or T-cell independent. 1- T-cell dependent antigen: Requires T cell help for B cell activation Example: proteins (microbial proteins or altered self proteins) 2- T-cell independent Ag: Activates B cells directly without help of T cells Example: polysaccharides (pneumococcal polysaccharide capsule, LPS).  T-cell Dependent T-cell Independent Antigen Antigen Structure Complex Simple Chemical Proteins, glycoprotein, Polysaccharide; nature and lipoproteins Lipopolysaccharide Antibody class - IgM (1ry immune Only IgM induced response) - IgA, IgG (2nd immune response) Immunological Yes No Memory Present in Yes No most (Exotoxin of all bacteria) (mainly in Gram’s Pathogens negative Bacteria)  Major Histocompatibility Complex (MHC) Glycoprotein present on the surface of all nucleated body cells. Encoded by MHC genes (present on short arm of chromosome number 6) and control self Ag presentation. In the past called HLA (human leucocyte Ag). Genes of MHC inherited from both parents giving new characteristic MHC for the individual like fingerprint. Each person has a unique characteristic MHC except identical twin which have the same MHC. Function: 1. Ag presentation 2. Role in transplantation 3. Role in autoimmune disease  Classification of MHC Molecules: N MHC Class I MHC Class II Distribution All nucleated cells of the Antigen presenting cells body (except RBCs) (macrophages, dendritic cells, B cells) Encoded by MHC class I genes MHC class II genes (HLA-A & HLA-B & (HLA-DR (SDL) & HLA- HLA-C) DP & HLA-DQ) Formed of - α-chain (α1 & α2 & α3) - α-chain (α1 &α2) - β2 microglobulin - β-chain (β1 &β2) Groove of Between α1 & α2 Between α1 & β1 Ag presentation Ag T cytotoxic (CD8) T helper (CD4) presented to